Mutlu Unal, Ikram M Arfan, Hofman Albert, de Jong Paulus T V M, Klaver Caroline C W, Ikram M Kamran
From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1698-702. doi: 10.1161/ATVBAHA.116.307545. Epub 2016 Jun 23.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage.
From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio [95% confidence interval] per SD increase in natural log-transformed NT-proBNP: 1.14 [1.03-1.27]). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP: -0.89 µm [-1.54 to -0.24]). This association remained unchanged after excluding participants with retinopathy signs.
In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease.
N末端B型利钠肽原（NT-proBNP）是心脏功能障碍的标志物，并且与大血管疾病的各种指标相关。然而，NT-proBNP是否也与微血管损伤有关仍不清楚。在一个社区居住人群中，我们研究了NT-proBNP与视网膜微血管损伤之间的关联。
基于鹿特丹研究，我们纳入了8437名无心血管疾病病史、有NT-proBNP数据和可分级视网膜图像的参与者（平均年龄64.1岁，59%为女性）。使用免疫测定法测量NT-proBNP血清水平。对眼底照片上出现的视网膜病变体征，即渗出物、微动脉瘤、棉絮斑和点状/斑状出血，在整个研究人群中进行分级；在研究人群的一个子样本（n = 2763）中半自动测量视网膜血管管径，即小动脉和小静脉管径。我们使用逻辑回归和线性回归模型对NT-proBNP与视网膜微血管损伤之间的关联进行横断面分析，并对年龄、性别和心血管危险因素进行了校正。我们发现NT-proBNP与视网膜病变的存在相关（自然对数转换后的NT-proBNP每增加1个标准差，校正比值比[95%置信区间]：1.14[1.03 - 1.27]）。我们还发现较高的NT-proBNP与较窄的小动脉管径相关（自然对数转换后的NT-proBNP每增加1个标准差，小动脉管径的校正平均差异：-0.89 µm[-1.54至-0.24]）。排除有视网膜病变体征参与者后，这种关联保持不变。
在无临床心血管疾病的参与者中，较高水平的NT-proBNP与视网膜微血管损伤相关，提示NT-proBNP作为小血管疾病标志物的潜在作用。
